FIRST STUDIES ON ANAPHYLAXIS 11 



them exhibited the characteristic symptoms, whilst 

 others did not shew any indisposition. 



To summarise these experiments, Otto concluded 

 that the toxin alone did not play any important part, 

 save to favour the production of hypersensitiveness ; 

 it was, however, clearly seen that the horse serum 

 was the essential cause of the phenomenon. Otto, 

 moreover, ascertained the fact that the phenomenon 

 only originated in those guinea-pigs which had first 

 been injected with a weak dose of the serum; and 

 that in guinea-pigs prepared by a mixture of the 

 serum and the diphtheria toxin death occurred in 

 50 per cent, of the cases. 



While fully admitting that he was in ignorance of 

 the mechanism of the phenomenon he described. 

 Otto pointed out the analogy between the pheno- 

 menon and the symptoms sometimes observed in 

 man following the injection of serum. 



About the same time two American scientists, 

 Rosenau and Anderson, published a very well authen- 

 ticated study entitled " On the Causes of Sudden 

 Death following the Injection of Horse Serum." 



To avoid repetition it is enough for us to say that 

 on broad lines their researches entirely accord with 

 those of Otto. They succeeded, moreover, in rendering 

 the guinea-pigs immune to anaphylactic symptoms by 

 injecting them with repeated massive doses of the 

 serum. We shall return to this point later. 



These authors almost succeeded in solving certain 

 other problems relating to anaphylaxis. Thus they 

 established the fact that between the time of sensi- 

 tisation of the guinea-pig and the time when the 

 animal is ripe for reaction to a second injection there 

 should elapse an incubation period of ten days. They 

 saw that in order to sensitise the guinea-pig a mini- 

 mum dose of serum (one-millionth of a cubic centi- 

 metre) was sufficient, and that once the state of 



